Polypeptide formation using pentamethyl guanidine as catalyst



United States Patent 1 2,930,780 POLYPEPTIDE FORMATION USING PENTA-METHYL GUANIDINE AS CATALYST Frederick John Weymouth, Coventry, England,assignor to Courtaulds Limited, London, England, a British company NoDrawing. Application January 6, 1958 Serial No. 707,130 Claims priority,application Great Britain February 22, 1955 1 Claim. (Cl. 260-775) Thisinvention relates to the production of polyamides.

This application is a continuation-in-part application of my applicationSer. No. 563,201, filed February 3, 1956.

This invention is particularly concerned with the production ofsynthetic polypeptides by polymerising anhydrocarboxyamino-acids havingthe general formula:

R being an alkyl or aralkyl group, which may be substituted with aninactive substituent group such as an ester group. Examples of suitableanhydrocarboxyamino acids are as follows, the R groups being indicatedin brackets:

The anhydrocarboxyamino acid of gamma-benzyl-L- glutamate (C H CHO-OC-CH -CH D', L and DL alanine (--CH,), of DL-beta-phenyl-alanine (C HCH of gamma-methyl-L-glutamate of leucine CHCH:-

0 a of isoleucine (CHr-C Ht-CH) of norleucine (CH CH -CH -CH ofepsilon-N carboxy-benzoxy lysine (C fl -CH -O-oc-NH-CH cH -cH -CH ofortho-acetyl tyrosine (om-o O-OOCHP) and also alpha-amino-N-butyricanhydrocarboxy amino The term polypeptide as used in this specificationmeans a polyamide built up with a recurrent R. where R, R and R arealkyl or aryl radicals, or Rf-O- where R, is an aryl radical, suchcompounds being primary amines, secondary amines and phenols.AGldSl'ldl/s merisation of anhydrocarboxyamino-acids.

V nitrobenzene,

In accordance with the present invention the polymerisation of one ormore anhydrocarboxyamino-acids is efiected in solution in thepresence ofpcnta-methyl guanidine. The penta-methyl guanidine is preferably addedto the anhydrocarboxyamino-acid as a solution for example in N-methylformamide.

The polymerisation of the anhydrocarboxyamino-acid is effected insolution. Suitable solvents are benzene, chlorbenzene, acetophenone,dioxane, methylene chloride, chloroform, dimethyl formamide and mixturesof these compounds, the actual choice of solvent depending on thesolubility properties of the original anhydrocarboxyamino-acid or acidsand the resulting polypeptide. The polymerisation can be carried out atvarying temperatures; temperatures ranging from 0100 C. have been usedsuccessfully. For economic reasons it is preferred to use ordinarytemperatures.

The invention is illustrated by the following example in which parts areby weight.

Example 5 parts of the N-carbonic anhydride of gamma-benzyl- L-glutamatewere dissolved in parts of dioxane. A solution of 0.032 part ofpentamethyl guanidine (1.32 mol percent based on the Weight of theanhydride) in 1 part of N-methyl formamide was addedwith stirring. Theresultant solution was stirred for 15 minutes at 25 C. in an evacuatedcontainer while a rapid evolution of carbon dioxide occurred. Thepolymer was precipitated by the addition of 2000 parts of ether.

The product obtained was a colourless fibre-forming polymer; its reducedviscosity in dichloracetic acid was 0.56. Reduced viscosity is given bywhere mm is the specific viscosity of a polymer solution having aconcentration (c) of 0.5 gram per 100 cc. of

solvent.

The procedure described in the example may be used for polymerisingother anhydrocarboxyamino acids such as the N-carbonic anhydride ofDL-fi-phenylalanine. I

What I claim is:

A process for the production of polyamides which alkyl and aralkylgroups and alkyl and aralkyl groups substituted by a group having thegeneral formula -COOX, where X is selected from the class consisting ofmethyl and benzyl groups and'pentamethyl guanidine as polymerisationinitiator, and maintaining the temperature of the resultant solution at0 C. to 100 C. whereby carbon dioxide is evolved and polymerisation ofthe anhydrocarboxyamino acid is effected.

References Cited in the file of this patent FOREIGN PATENTS 675,298Great Britain Ju1 9, 1932;"

